Use of drugs, tobacco, and alcohol starts earlier among American Indian adolescents than in many other groups in the U.S. and early use is a clear marker of risk for prolonged and problematic use. Significant disparities in substance use problems, including abuse and dependence, are well documented. Yet despite numerous prevention efforts in response to these disparities, they remain pronounced. Our goal is to better understand emergent substance use among young adolescent American Indians and identify risk and protective factors that may provide windows of opportunity for prevention. Using theories emanating from research with other populations, supplemented with what we know about substance use among older American Indians, we have identified an integrative framework for understanding early substance use development in this population. This framework incorporates the effects of stressful life events and early puberty, mediated by peer influences, and moderated by both parenting and cultural factors;our work will explore both the unique and combined effects of these factors on early substance use. While some of this array of influences have been examined among American Indians (stress, peers, culture), others have received little more than cursory attention (early puberty, parenting). Thus, much work remains to be done to inform the kind of empirically based prevention programs that are likely to be successful for young adolescents in American Indian communities. We have a unique opportunity to explore these influences on early substance use in a reservation community that has particularly high rates of substance problems, building on a longitudinal evaluation of a sexual risk prevention program that we are currently implementing in this community. In designing the survey instrument for the sexual risk study, we took advantage of the opportunity to include measures relevant to early substance use as well;thus, we now have data in hand that will allow us an unprecedented look at early substance use development in this population. We will address the following 4 Specific Aims: 1) Extend descriptions of the development of drug, tobacco, and alcohol use among American Indian youth into early adolescence;2) estimate the relationship between stressful events and early substance use development in this population;3) determine whether early puberty has an important relationship to early substance use;explore how early puberty interacts with other stressors to impact risk and how deviant peer influences mediate these links;and 4) explore how parenting and connection to tribal culture modify risk for early adolescent substance use. This work will address a significant problem in a high-risk and understudied population, use an approach that capitalizes on extant data, and build on existing models of substance use development in innovative ways that promise to move the field forward. PUBLIC HEALTH RELEVANCE: Youth in the tribal community targeted in this study are at relatively greater risk than others in the U.S. for developing substance use problems. As we learn more about how these problems emerge in early adolescence in this population, we will be better equipped to determine optimal timing and strategies for preventive intervention efforts. This work will also contribute to theoretical models of substance use development and broaden our understanding of factors related to early use, with likely implications for other populations as well.